Infective Endocarditis as a complication of COVID-19 infection; A case report and review of literature

COVID-19 has been known to induce systemic inflammation and hyper coagulate state leading to different complications. Cardiovascular complications are one of the most important among complications following COVID-19 infection. A 57 years old woman with past medical history of COVID-19 infection about two months ago came to our hospital with presentation of fever and dyspnea. During workup, tricuspid valve infection associated with pulmonary septic emboli was diagnosed without any obvious risk factor for infective endocarditis. It seems that COVID-19 infection may increase the rate of endocarditis in patients with or without risk factors of endocarditis.

with lethargy and loss of appetite and in outpatient visit.Then, antibiotic was prescribed for her but the fever persisted and she developed dyspnea.She also had a history of Diabetes Mellitus (DM), Hypertension (HTN) and hypothyroidism being on oral medication.
According to the patient's history, we considered complications of COVID-19 infection including cardiac involvement or pneumonia that complicating the pulmonary emboli.
The results of initial laboratory tests showed leukocytosis (White Blood Cells: 18000 per microliter) with 82% neutrophils, Erythrocyte Sedimentation Rate (ESR):42mm/hour and C-Reactive Protein (CRP) was elevated.The blood cultures were also taken from two different sites and were negative.COVID-19 PCR test was done and was negative.Electrocardiogram (ECG) revealed sinus tachycardia, left axis deviation and evidence of Left Ventricular Hypertrophy (LVH).In echocardiography, left ventricular Ejection Fraction was normal with mild LVH with no wall motion abnormality.But a large (2.9 *0.8cm) mobile heterogeneous echo density was seen on atrial side of Tricuspid Valve (TV) that resulted in destruction of TV with severe Tricuspid Regurgitation (TR) in favor of vegetation.(Figure 2, Supplementary File 4, Video 4).
Chest CT revealed scattered nodules in both lungs with several consolidation and peripheral ground glass opacities (halo sign) in both upper and lower lobs of the lung suggestive of septic emboli.In addition, sub segmental collapse consolidation in base of Right Lower Lobe and mild pleural effusion in right side were seen.(Figure 3, Supplementary Files, Video 5, 6)  According to modified Duke Criteria for infective endocarditis, the patient had one major and two minor criteria for IE.So the patient underwent experimental treatment of infective endocarditis with Meropenem and Vancomycine but despite anti-biotic therapy, the patient's fever persisted.In lab data, WBC count of 2100 and ESR level of 81 were found.She underwent echocardiography again and no change in size of vegetation or no evidence of abscess formation was seen.Considering fever and vegetation size, the patient was scheduled for surgical excision of vegetation on TV with valve replacement.Intraoperative observation reported large vegetation associated with destructed valve; so it was replaced by a mechanical bileaflet prosthetic valve.
The native valve tissue specimen was sent for pathologic examination and showed hyalinization, congestion and calcification with extensive necrosis, hemorrhage and foci of inflammatory cells infiltration.These microscopic findings were indicative of endocarditis.(Figure 4) Two days after surgery, the patient developed bradycardia and the ECG showed Complete Heart Block (CHB).Then, a temporary pace maker was implanted, soon replaced by a permanent epicardial one.Post-op transthoracic echocardiography showed good function of tricuspid prosthetic valve with no residual vegetation.The patient was discharged home after completion of antibiotic course and was uneventful in her follow up.

Discussion
Following the outbreak of COVID-19 disease, its adverse effects were also commonly reported.Its cardio-vascular complications including acute coronary syndrome, atrial fibrillation, ventricular arrhythmia, myocarditis, pericarditis, hyper coagulate state and pulmonary thrombo-embolism, are one of the most important complications of COVID-19 infection.Although in some centers, an increased incidence of endocarditis has been reported during first months of COVID-19 pandemic 4 due to immunosuppressive therapies, central venous or urinary catheterization; some others showed decreased rate of endocarditis in this period. 5scolà-Vergé et al examined the incidence of endocarditis between 2019 and 2 months of 2020 (in the early months of outbreak of COVID-19).They concluded that the reduced rate of IE in 2020 compare to 2019, may be related to instruction to stay at home, peoples fear of infection in medical facilities and avoiding medical cares in pandemic, overlap between symptoms of endocarditis and COVID infection and the prescription of oral antibiotics without further examination. 6However, their study was performed at the beginning of the covid-19 pandemic and over time, more cases of endocarditis were reported.
Currently, there is several case reports of endocarditis associated with COVID infection.In May 2020, Amir et al reported the first case of concomitant COVID infection with infective endocarditis that involving mitral valve in a patient with Rheumatic Heart Disease. 7][11] Tricuspid valve infection is relatively uncommon and usually occurs in patient with risk factors.Until now two cases of TV endocarditis were reported in context of COVID infection.One of them was in a patient with history of trauma that presented with severe respiratory distress and positive test for SARS-CoV-2 and another one was in a intubated COVID patient with central venous catheter. 12,13he important point about these cases is that in most of them, there were several risk factors for bacteremia and IE like central venous lines, urinary catheters, mechanical ventilation, RHD, and mechanical valve.Moreover, many of them had been received immunosuppressive therapies for COVID infection; although it's not clear that these treatments increase risk of endocarditis or not.
But in the present case with TV endocarditis, there is not any classic risk factor for IE.In her past medical history, she only had a history of mild COVID-19 infection that complicated with pulmonary emboli.Therefore, she did not receive immunosuppressive therapy in her disease course nor central venous or urinary catheter was fixed for her.We justified negative blood culture as a result of outpatient antibiotic treatment.In addition, late presentation of endocarditis is very important in this case.All mentioned IE cases in previous part were developed during COVID 19 disease course but in our case IE was diagnosed 2 months after COVID 19.Similarly, Kumanayaka et al reported a case of mitral valve endocarditis one month after COVID infection in a patient without IE risk factor rather than history of coronavirus 19 and treatment with dexamethasone. 3 Alizadehasl et al also reported a case of prosthetic mitral IE 3weeks after COVID infection. 14So, it seems that the role of COVID 19 could not be ruled out as a predisposing factor for IE either early or late.Even though many of reported cases had other risk factors, but some others like our case didn't have any obvious risk factor for IE other than COVID infection and this hypothesis is highlighted by the study of Aikawa et al who reported evidence of late onset non-bacterial endocarditis following COVID 19 infection in imaging and biopsy. 15t seems that systemic inflammation and hyper coagulate state induced by COVID-19 infection, may be responsible for its complications including IE.

Conclusion
It seems that covid-19 infection may increase the rate of endocarditis in patients with or without risk factors of endocarditis.So, in patients with Covid-19, if the fever persists or evidence of septic embolism are seen in imaging, we should consider the complications of the disease, especially endocarditis.In addition, we should be careful about selecting patients for hospitalization, implantation of venous lines or urinary catheters and immunosuppressive treatment to reduce rate of endocarditis.

Figure 1 .Figure 3 .
Figure 1.chest CT angiography that showed filling defects in sub segmental branches of basal segment of both pulmonary arteries (left side here) in favor of pulmonary emboli associated with sub segmental collapse consolidation in base of both lungs